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适应性免疫在清除新冠病毒和保护感染中的作用Correlate of protection from SARS-CoV-2

已有 797 次阅读 2021-9-6 16:46 |系统分类:论文交流

  在疫苗诱导的免疫和自然感染诱导的机体免疫反应中,细胞免疫和体液免疫在清除 SARS-CoV-2 和防止新冠病毒再感染方面的相对贡献仍然不明确。The relative contributions of cellular and humoral immunity in the clearance of SARS-CoV-2 and protection from reinfection remain poorly defined in both vaccine-induced immunity and natural infection-induced immunity1. The identification of immune correlates of protection will facilitate the development of effective vaccines. 

    AKIKO IWASAKI 课题组利用小鼠模型证明:先天免疫不足以清除新冠病毒感染,这可能是由于SARS-CoV-2对干扰素途径的拮抗作用。 CD4+ 细胞毒性 T 细胞在初次感染期间在病毒清除中不起主要作用,而抗体促进 CD4+ T 细胞在清除急性感染中起重要作用。 此外,他们发现恢复期的小鼠或接种 mRNA 疫苗的小鼠都可以免受同源病毒和变体病毒B.1.351(Beta)的感染。 此外,这种保护作用主要由抗体反应介导,是细胞免疫介导。 这些结果突出了疫苗和自然感染诱导的抗体的保护作用1。Innate immunity is insufficient to clear infection, which may be due to antagonism of interferon pathway by the virus.  CD4+ cytotoxic T cells do not play a major role in viral clearance during primary infection, whereas antibody promoting CD4+ T cells play an improtant role in clearance of acute infection.  Furthermore, they find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351 (Beta). Additionally, this protection largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection1

    总之,该研究为病毒清除和保护的免疫决定因素提供了新见解。 虽然 T 细胞在清除原发感染中很重要,但它们对于防止再新冠病毒感染或疫苗介导的保护并不需要,这可能是由于足够的抗体介导的免疫。

     In conclusion, this study provide insights into both the immunologic determinants of viral clearance and protection. While T cells were important in the clearance of primary infection, they were not required for protection against reinfection or vaccine-mediated protection, likely due to sufficient antibody-mediated immunity. These results are reassuring as they indicate that a robust humoral immune response is sufficient even in the setting of decreased neutralizing capacity. These results also have important public health and vaccine development implications, as they suggest that antibody mediated immunity may be a sufficient correlate of protection1

    最近多项研究表明,中和抗体水平可以作为反应COVID-19 疫苗的保护作用的指标3-7

    Recent studies suggest that neutralizing antibodies could serve as a correlate of protection for vaccines against SARS-CoV-2 in humans3. Vaccine-induced immune responses are often multifaceted, but single components such as antibody responses may correlate with the level of protection. In fact, most of the currently accepted correlates of protection are based on antibody measurements3.


   建立抗体滴度作为保护的相关性, 并定义保护滴度, 对于公共卫生考虑和患者管理极为重要。确定体液免疫中抗体的保护性滴度应该是未来研究自然感染或疫苗接种提供的保护的优先事项2

    Establishment of antibody titres as a correlate of protection and defining a protective titre would be extremely important for public health considerations and for patient management. A correlate of protection and a protective threshold would also allow for the development of additional SARS-CoV-2 vaccines based on small immunogenicity-based phase 3 trials rather than large and costly field efficacy trials, which are becoming exceedingly difficult to perform. Determination of a protective titre should be a priority for future studies that investigate protection afforded by natural infection or vaccination2.


参考文献:

1. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2

Science Immunology . https://www.science.org/doi/10.1126/sciimmunol.abl4509 


2. Correlates of protection from SARS-CoV-2 infection. Lancet.  https://doi.org/10.1016/S0140-6736(21)00782-0 


3. A correlate of protection for SARS-CoV-2 vaccines is urgently needed. Nat Med 27, 1147–1148 (2021). https://doi.org/10.1038/s41591-021-01432-4  


4. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 27, 1205–1211 (2021). https://doi.org/10.1038/s41591-021-01377-8 


5. Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine . https://doi.org/10.1016/j.vaccine.2021.05.063 


6. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. SCIENCE  https://www.science.org/doi/full/10.1126/science.abj0299 


7. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature. 

 https://pubmed.ncbi.nlm.nih.gov/33276369/  



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